Improved overall survival with Gemtuzumab Ozogamicin (GO) compared with best supportive care (BSC) in elderly patients with untreated acute myeloid leukemia (AML) not considered fit for intensive chemotherapy: final results from the randomized phase III study (AML-19) of the EORTC and gimema leukemia groups

peer reviewe

Prognostic impact of genetic characterization in the GIMEMA LAM99P multicenter study for newly diagnosed acute myeloid leukemia

Recent advances in genetic characterization of acute myeloid leukemia indicate that combined cytogenetic and molecular analyses provide better definition of prognostic groups. The aim of this study was to verify this prospectively in a large group of patients

Chimeric Antigen Receptor T-cell Therapy in Hematologic Malignancies and Patient-reported Outcomes: A Scoping Review

The inclusion of patient-reported outcome (PRO) measures in chimeric antigen receptor (CAR) T-cell therapy research is critical for understanding the impact of this novel approach from a unique patient standpoint. We performed a scoping review to map the available literature on the use of PRO measures in CAR T-cell therapy studies of patients with hematologic malignancies published between January 2015 and July 2022. Fourteen studies were identified, of which 7 (50%) were investigational early-phase trials, 6 (42.9%) were observational studies, and 1 (7.1%) was a pilot study. The EQ-5D and the PROMIS-29 were the 2 most frequently used PRO measures, being included in 6 (42.9%) and 5 (35.7%) studies, respectively. Despite differences in study designs, there seems to be evidence of improvements over time since CAR T-cell infusion in important domains such as physical functioning and fatigue, at least in patients who respond to therapy. Overall, the studies identified in our review have shown the added value of PRO assessment in CAR T-cell therapy research by providing novel information that complements the knowledge on safety and efficacy. However, there are several questions which remain to be answered in future research. For example, limited evidence exists regarding patient experience during important phases of the disease trajectory as only 4 (28.6%) and 5 (35.7%) studies provided information on PROs during the first 2 weeks from CAR T-cell infusion and after the first year, respectively. Time is ripe for a more systematic implementation of high-quality PRO assessment in future clinical trials and in real-life settings of patients treated with CAR T-cell therapy

Exploring cost-benefit analysis of research, development and innovation infrastructures: an evaluation framework

Governments, funding agencies and policy makers have high expectations on research, development and innovation (RDI) infrastructures in the context of science and innovation policies aimed at sustaining economic growth in the long term. The stakes associated with their selection and evaluation are therefore high. Cost-benefit analysis of RDI infrastructures is a new field. The intangible nature of some benefits and the uncertainty associated to the achievement of research results have often discouraged the use of a proper CBA for RDI infrastructures. Recently, some attempts to develop a CBA theoretical framework for RDI infrastructures have been made in the context of the use of Structural Funds by the Czech government and JASPERS. Moreover, the new Guide for the CBA of investment projects in the context of Cohesion Policy, recently adopted by the European Commission (2014) provides guidelines to appraise RDI projects, but also admits that \u2013 due to lack of experience and best practices \u2013 further steps are needed to improve the evaluation framework. This paper presents the results and the lessons learned on how to apply ex-ante CBA for major RDI infrastructures by a team of economists and scientists at the University of Milan and CSIL during a three-year research project supported by a EIBURS grant of the European Investment Bank Institute. Albeit the comprehensive conceptual framework presented in the paper builds on principles firmly rooted in CBA tradition, their application to the RDI sector is still in its infancy. So far, the model has been applied on two cases in physics involving particle accelerators (the Large Hadron Collider (LHC) at CERN and the National Centre for Oncological Treatment (CNAO) in Italy)). In a nutshell, the model presented break down benefits into two broad classes: i) use benefits, held by different categories of infrastructure\u2019s users such as scientists, firms, students and general public visitors, and ii) non-use benefits, denoting the social value for the discovery potential of the RDI infrastructure regardless of its actual or future use. We argue that the social value of discovery can be estimated with contingent valuation techniques. Another significant feature of our approach is the stochastic nature of the CBA model, intended to deal with the uncertainty and risk of optimism bias in the estimates

Patient-reported outcomes as independent prognostic factors for survival in oncology:systematic review and meta-analysis

Objectives: Assessment of patient-reported outcomes (PROs) in oncology is of critical importance because it provides unique information that may also predict clinical outcomes. Methods: We conducted a systematic review of prognostic factor studies to examine the prognostic value of PROs for survival in cancer. A systematic literature search was performed in PubMed for studies published between 2013 and 2018. We considered any study, regardless of the research design, that included at least 1 PRO domain in the final multivariable prognostic model. The protocol (EPIPHANY) was published and registered in the International Prospective Register of Systematic Reviews (CRD42018099160). Results: Eligibility criteria selected 138 studies including 158 127 patients, of which 43 studies were randomized, controlled trials. Overall, 120 (87%) studies reported at least 1 PRO to be statistically significantly prognostic for overall survival. Lung (n = 41, 29.7%) and genitourinary (n = 27, 19.6%) cancers were most commonly investigated. The prognostic value of PROs was investigated in secondary data analyses in 101 (73.2%) studies. The EORTC QLQ-C30 questionnaire was the most frequently used measure, and its physical functioning scale (range 0-100) the most frequent independent prognostic PRO, with a pooled hazard ratio estimate of 0.88 per 10-point increase (95% CI 0.84-0.92). Conclusions: There is convincing evidence that PROs provide independent prognostic information for overall survival across cancer populations and disease stages. Further research is needed to translate current evidence-based data into prognostic tools to aid in clinical decision making.</p

Cost-benefit analysis of applied research infrastructure : Evidence from health care

The present study aims at offering empirical evidence to improve existing knowledge and theory building on research infrastructure evaluation. Through an inductive case study research strategy, an innovative cost-benefit analysis framework has been used to assess the impact of an applied research infrastructure. The case study is the National Hadrontherapy Centre for Cancer Treatment (CNAO) located in Pavia (Italy). CNAO is an applied research facility specialised in hadrontherapy, an advanced oncological treatment showing clinical advantages as compared to traditional radiotherapy, at the same time being more expensive as it exploits non-commercial accelerators technology and sophisticated control and dose delivery systems. The analysis shows that with a fairly high probability the Centre provides a positive net contribution to society's welfare. Source of benefits are mainly health treatments to patients, for whom gains in terms of longer or better lives are guaranteed as compared to a counterfactual situation where they are treated with conventional therapies or they have no alternatives. Such benefits are the direct consequences of the application to end users of the knowledge developed in the Centre with research activities and are quantified and assessed on the basis of conventional cost-benefit analysis (CBA) approaches for health benefits. Additional benefits generated by the Centre are typical of research infrastructures in different scientific domains and refer to technological spillovers (namely creation of spin-offs, technological transfer to companies in the supply chain and to other similar facilities), knowledge creation (production of scientific outputs), human capital formation (training of doctoral students, technicians and professionals in the field of hadrontherapy) and cultural outreach (students, researchers and wider public visiting the facilities). Evidences show that the adopted CBA framework is a promising avenue as compared to existing alternative methodologies informing decision-making. Further research is however needed to fine tune the methodology, in particular for what concerns technological spillovers and knowledge creation benefits

Prognostic impact of KMT2A-AFF1-positivity in 926 BCR-ABL1-negative B-lineage acute lymphoblastic leukemia patients treated in GIMEMA clinical trials since 1996

The impact of KMT2A-AFF1 rearrangement in pediatric-like, minimal residual disease (MRD)-based clinical trials and the effect of transplant in KMT2A-AFF1 ALL are still debated

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p&lt;0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p&lt;0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p&lt;0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue

Fatigue in newly diagnosed acute myeloid leukaemia: General population comparison and predictive factors

Objectives: This study compared the burden of fatigue between treatment-naïve patients with newly diagnosed acute myeloid leukaemia (AML) and the general population and investigated patient factors associated with fatigue severity. Methods: Pretreatment patient-reported fatigue was assessed with the Functional Assessment of Chronic Illness Therapy-Fatigue questionnaire in a sample of 463 newly diagnosed patients with AML who were enrolled in a clinical trial. Multivariable linear regression models were used to estimate the adjusted mean differences in fatigue between patients with AML and adults from the general population (n=847) by AML disease risk categories. A clinically meaningful difference in fatigue was defined as ≥3 points. Univariable and multivariable linear regression models were used to identify sociodemographic, clinical and molecular correlates of worse fatigue in patients with AML. Results: Patients with AML reported adjusted mean fatigue scores that were 7.5 points worse than the general population (95% CI -8.6 to -6.4, p&lt;0.001). Across AML disease risk categories, adjusted mean differences in fatigue compared with the general population ranged from 6.7 points worse (patients with favourable risk: 95% CI -8.6 to -4.8, p&lt;0.001) to 8.9 points worse (patients with poor risk, 95% CI -10.5 to -7.2, p&lt;0.001). Overall, 91% of patients with AML reported fatigue that was equal to or worse than the general population's median fatigue score. Higher pretreatment fatigue was independently associated with female sex, WHO performance status ≥1 and lower platelet levels. Conclusions: Patients with newly diagnosed AML reported worse fatigue than the general population, and mean differences exceeded twice the threshold for clinical significance. Our findings may help to identify patients with AML most likely to benefit from supportive care interventions to reduce fatigue